MARCKS‐dependent mucin clearance and lipid metabolism in ependymal cells are required for maintenance of forebrain homeostasis during aging

Aging Cell

Nagendran Muthusamy³  Laura J. Sommerville³  Adam J. Moeser⁴  Deborah J. Stumpo¹  Philip Sannes³  Kenneth Adler³  Perry J. Blackshear¹  Jill M. Weimer² 

[1] Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Durham, NC, USA;Sanford Research, Children's Health Research and Department of Pediatric, University of South Dakota Sanford School of Medicine, Sioux Falls, SD, USA;Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA;Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA

关键词: aging;    barrier function;    Clca3;    cerebral cortex;    ependymal cells;    lipid droplets;    mucin;    oxidative stress;   

DOI  :  10.1111/acel.12354

来源: Wiley

【 摘 要 】

Summary

Ependymal cells (ECs) form a barrier responsible for selective movement of fluids and molecules between the cerebrospinal fluid and the central nervous system. Here, we demonstrate that metabolic and barrier functions in ECs decline significantly during aging in mice. The longevity of these functions in part requires the expression of the myristoylated alanine-rich protein kinase C substrate (MARCKS). Both the expression levels and subcellular localization of MARCKS in ECs are markedly transformed during aging. Conditional deletion of MARCKS in ECs induces intracellular accumulation of mucins, elevated oxidative stress, and lipid droplet buildup. These alterations are concomitant with precocious disruption of ependymal barrier function, which results in the elevation of reactive astrocytes, microglia, and macrophages in the interstitial brain tissue of young mutant mice. Interestingly, similar alterations are observed during normal aging in ECs and the forebrain interstitium. Our findings constitute a conceptually new paradigm in the potential role of ECs in the initiation of various conditions and diseases in the aging brain.

【 授权许可】

CC BY   
© 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.